Published Online
on November 20, 2006

A more recent version of this article appeared on January 1, 2007

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Submitted on June 23, 2006
Revised on July 17, 2006

Intrarenal Dopamine D₁-Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

Leslie J. Salomone; Nancy L. Howell; Helen E. McGrath; Brandon A. Kemp; Susanna R. Keller; John J. Gildea; Robin A. Felder; and Robert M. Carey^*

From the Division of Endocrinology and Metabolism, Department of Medicine (L.J.S., N.L.H., H.E.M., B.A.K., S.R.K., R.M.C.), and the Department of Pathology (J.J.G., R.A.F.), University of Virginia Health System, Charlottesville.

^* To whom correspondence should be addressed. E-mail: rmc4c{at}virginia.edu.

Abstract--We explored the effects of direct renal interstitial stimulation of dopamine D₁-like receptors with fenoldopam, a selective D₁-like receptor agonist, on renal sodium excretion and angiotensin type-2 (AT₂) receptor expression and cellular distribution in rats on a high-sodium intake. In contrast to vehicle-infused rats, sodium excretion increased in fenoldopam-infused rats during each of three 1-hour experimental periods (<0.001). Blood pressure was unaffected by vehicle or fenoldopam. In plasma membranes of renal cortical cells, fenoldopam increased D₁ receptor expression by 38% (P<0.05) and AT₂ receptor expression by 69% (P<0.01). In plasma membranes of renal proximal tubule cells, fenoldopam increased AT₂ receptor expression by 108% (P<0.01). In outer apical membranes of proximal tubule cells, fenoldopam increased AT₂ receptor expression by 59% (P<0.01). No significant change in total AT₂ receptor protein expression was detectable in response to fenoldopam. Fenoldopam-induced natriuresis was abolished when either PD-123319, a specific AT₂ receptor antagonist, or SCH-23390, a potent D₁-like receptor antagonist, was coinfused with F (P<0.001). In summary, direct renal D₁-like receptor activation increased urinary sodium excretion and the plasma membrane expression of AT₂ receptors in renal cortical and proximal tubule cells. D₁-like receptor-induced natriuresis was abolished by intrarenal AT₂ receptor inhibition. These findings suggest that dopaminergic regulation of sodium excretion involves recruitment of AT₂ receptors to the outer plasma membranes of renal proximal tubule cells and that dopamine-induced natriuresis requires AT₂ receptor activation.

Key words: angiotensin • dopamine • receptors • sodium excretion • natriuresis • receptor trafficking • kidney

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